Porcine epidemic diarrhea virus ORF3 protein causes endoplasmic reticulum stress to facilitate autophagy

Veterinary Microbiology
Dehua ZouHongwei Cao

Abstract

Porcine epidemic diarrhea virus (PEDV), the causative agent of PED, is an enveloped, positive-stranded RNA virus in the genus Alphacoronavirus, family Coronaviridae, order Nidovirales. PEDV non-structural accessory protein ORF3 is an ion channel related to viral infectivity and pathogenicity. Our previous study showed that PEDV ORF3 has expression characteristic of aggregation in cytoplasm, but its biological function remains elusive. Thus in this study, we initiated the construction of various vectors to express ORF3, and found ORF3 localized in the cytoplasm in the aggregation manner. Subsequently, confocal microscopy analysis showed that the aggregated ORF3 localized in endoplasmic reticulum (ER) to trigger ER stress response via up-regulation of GRP78 protein expression and activation of PERK-eIF2α signaling pathway. In addition, our results showed that PEDV ORF3 could induce the autophagy through inducing conversion of LC3-I to LC3-II, but couldn't influence the apoptosis. In contrast, conversion of LC3-I/LC3-II could be significantly inhibited by 4-PBA, an ER stress inhibitor, indicating that ORF3-induced autophagy is dependent on ER stress response. This work not only provides some new findings for the biological functio...Continue Reading

Citations

Aug 28, 2020·Frontiers in Microbiology·Katia FecchiAnna Ruggieri
May 15, 2020·Pathogens·Shasha LiHaixue Zheng
Dec 1, 2020·Autophagy·Marie-Angela DomdomBaharia Mograbi
Jun 21, 2020·European Journal of Pharmacology·Antoni SuredaSaeid Ghavami
Feb 3, 2021·International Journal of Molecular Sciences·Nicholas A Wong, Milton H Saier
Oct 5, 2020·Microbial Pathogenesis·Zhiwei LiShuqi Xiao
May 18, 2021·Frontiers in Cellular and Infection Microbiology·Elisa B PrestesLeticia A M Carneiro
Sep 2, 2021·Future Microbiology·Aref MovaqarSaman Soleimanpour
Oct 14, 2021·Microbiology and Molecular Biology Reviews : MMBR·Evelyne KohliCarmen Garrido

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Methods Mentioned

BETA
confocal microscopy
transfection
flow cytometry

Software Mentioned

TMHMM
ImageJ
Cellquest
Adobe Photoshop

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